Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation

Cremophor EL (CrEL) is a formulation vehicle used for various poorly-water soluble drugs, including the anticancer agent paclitaxel (Taxol). In contra st to earlier reports, CrEL is not an inert vehicle, but exerts a range of biological effects, some of which have important clinical implications. Its use has been associated with severe anaphylactoid hypersensitivity reactio ns, hyperlipidaemia, abnormal lipoprotein patterns, aggregation of erythroc ytes and peripheral neuropathy. The pharmacokinetic behaviour of CrEL is do se-independent, although its clearance is highly influenced by duration of the infusion. This is particularly important since CrEL can affect the disp osition of various drugs by changing the unbound drug concentration through micellar encapsulation. In addition, it has been shown that CrEL, as an in tegral component of paclitaxel chemotherapy, modifies the toxicity profile of certain anticancer agents given concomitantly, by mechanisms other than kinetic interference. A clear understanding of the biological and pharmacol ogical role of CrEL is essential to help oncologists avoid side-effects ass ociated with the use of paclitaxel or other agents using this vehicle. With the present development of various new anticancer agents, it is recommende d that alternative formulation approaches should be pursued to allow a bett er control of the toxicity of the treatment and the pharmacological interac tions related to the use of CrEL. (C) 2001 Elsevier Science Ltd. All rights reserved.